Unit:
Department of NursingLibrary of the School of Health Sciences
Author:
Ryakiotakis Ermis
Dissertation committee:
Σταματάκης Αντώνιος, Καθηγητής, Τμήμα Νοσηλευτικής, ΕΚΠΑ
Κιτράκη Ευθυμία, Καθηγήτρια, Τμήμα Οδοντιατρικής, ΕΚΠΑ
Δάλλα Χριστίνα, Αναπληρώτρια Καθηγήτρια, Τμήμα Ιατρικής, ΕΚΠΑ
Στυλιανοπούλου Φωτεινή, Ομότιμη Καθηγήτρια, Τμήμα Νοσηλευτικής, ΕΚΠΑ
Σκαλιώρα Ειρήνη, Καθηγήτρια , Τμήμα Ιστορίας & Φιλοσοφίας της Επιστήμης, ΕΚΠΑ
Σιδηροπούλου Κυριακή, Αναπληρώτρια Καθηγήτρια, Ινστιτούτο Μοριακής Βιολογίας & Βιοτεχνολογίας, ΙΤΕ
Φρουδαράκης Εμμανουήλ, Επίκουρος Καθηγητής, Ινστιτούτο Μοριακής Βιολογίας & Βιοτεχνολογίας, ΙΤΕ
Original Title:
Η επίδραση των πρώιμων εμπειριών και της κοινωνικής αλληλεπίδρασης στο σύστημα ανταμοιβής σε επίμυς
Translated title:
The effects of early-life experiences and social interactions on the reward system of the rat
Summary:
Adverse early life experiences affect neuronal growth and maturation of reward circuits that modify behavior under reward predicting conditions. Previous studies in our lab have demonstrated that rats undergoing denial of expected reward in the form of maternal contact (DER-animal model of maternal neglect) during early post-natal life developed anhedonia, aggressive play-fight behaviors and aberrant prefrontal cortex structure and neurochemistry. Although many studies have revealed social deficiencies following early-life stress, most reports focus on individual animal tasks. Thus, attention needs to be given to the behavioral effects of group tasks and the contribution of the social aspects to the behavioral profile of animals afflicted by early life adversity.
To investigate these effects, we designed a 2-phase experimental setup. During the first experimental phase we investigated the potential impact of the DER experience on the manifestation of behavioral responses induced by natural rewards. Thus, we evaluated: 1) naïve adult male sexual preference and performance, and 2) anticipatory behavior during a grouped 2-phase food anticipation learning task (FA) composed of a context-dependent (CoP) and a cue-dependent learning period (CuP).
During the second experimental phase we investigated whether the DER phenotype is determined, in addition to the adverse neonatal experience, by negative every day social interactions from weaning until adulthood. To this end, we evaluated the behavior of animals raised in mixed rearing conditions of DER and CTR animals, in tasks that were found to be affected by the DER experience during the first experimental phase. Mixed rearing groups were 3C (3 CTR rats), 2C1D (2CTR rats (2C) reared with 1DER (1D)), 1C2D (1CTR rat (1C) reared with 2DER (2D) and 3D (3 DER rats).
Results from the first experimental phase showed that DER rats spent a normal amount of time in the vicinity of and efficiently initiated sexual intercourse with receptive females, suggesting an intact sexual reward motivation and consummation. On the contrary, during the context-dependent phase of food anticipation training DER rats displayed a modified exploratory activity and lower overall reward-context association. Moreover, during the cue-dependent phase DER rats displayed a mild deficit in context-reward association while increased cue-dependent locomotion. Additionally, DER rats displayed unstable food access priority following food presentation, after the end of FA training. These abnormal behaviors were accompanied by overactivation of the ventral prefrontal cortex and nucleus accumbens, as assessed by pCREB levels.
During the second experimental phase we assessed the effects of mixed rearing conditions on the occurrence of the DER phenotype during FA training. We found that in mixed rearing conditions the presence of CTR animals was beneficial for DER animals: Reward association deficiencies were ameliorated in 2D animals while animals of the 1D category displayed improved reward seeking and a mildly enhanced reward association compared to 3C. In contrast, mixed rearing resulted in negative effects for CTR animals: 2C animals displayed mild delays in reward learning while the 1C animals were characterized by lower mobility and slower reward learning. Albeit this reward learning deficiency was less severe compared to animals that lived in pure DER rearing conditions. Interestingly animals in mixed rearing groups seemed to establish stable food approach hierarchy with the DER animals occupying higher dominancy positions. Interestingly, we showed that pCREB levels in the vPFC and NAc of animals in mixed rearing groups were comparable to the CTR rearing group, indicating that mixed rearing conditions normalized aberrant brain activation during FA training.
Collectively, our data show that the neonatal DER experience resulted in adulthood in altered activation of the reward circuitry, thus interfering with the normal formation of environmental cues-reward associations, possibly due to disrupted hierarchy formation. These findings provide additional evidence for the deleterious effects of early life adversity on reward system, social hierarchy formation, and brain function. Mixed rearing with normal animals ameliorated the negative effects of the DER experience on reward association learning, hierarchical instability and abnormal brain activation. Conversely, mixed rearing with DER animals affected negatively reward learning and social status in the CTR animals.
In conclusion, this study indicated that: a) Early life adversity induces social instability which initiates a vicious cycle of everyday social stress affecting animals reared in groups while b) resocializing in a normal social environment following weaning can ameliorate the manifestation of early-life stress long-term effects.
Main subject category:
Health Sciences
Keywords:
Early-life adverse experiences, Social interactions, Reward circuit, vPFC, NAC, Reward-associated behaviors, pCREB
Number of references:
685
File:
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Ryakiotakis_Ermis_Thesis.pdf
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File access is restricted until 2025-02-16.
